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This study aims to evaluate the electrocardiogram (ECG) effects of Sancuso® compared to placebo and moxifloxacin in healthy subjects.

Condition or disease

Intervention/treatment

Phase

Healthy

Drug: granisetron

Phase 1

Detailed Description:

Granisetron is a well tested and established 5-HT3 receptor antagonist used in both oral and intravenous (IV) forms. A transdermal form of granisetron (Sancuso®) was approved by the United States (US) Food and Drug Administration (FDA) in September 2008.

Many of the 5-HT3 antagonists were developed and approved before the adoption of the International Conference on Harmonisation (ICH) E14 standard on QTc and cardiac testing. The association of non-cardiac medicinal products with the potential to prolong the QT interval and induce torsades des pointes (TdP) has significant implications for the future development of medicinal products.

Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3

Other Names:

Granisetron Transdermal System

Sancuso® patch

Kytril®

Granisetron Injection

IV Placebo (0.9% saline)

Placebo patches

Avelox® Oral

Experimental: Treatment B: IV Granisetron 10 mcg/kg

Treatment B: placebo patch (Day 1) and granisetron IV (Day 3)

Drug: granisetron

Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3

Other Names:

Granisetron Transdermal System

Sancuso® patch

Kytril®

Granisetron Injection

IV Placebo (0.9% saline)

Placebo patches

Avelox® Oral

Placebo Comparator: Treatment C: Matching placebo patch

Treatment C: placebo patch (Day 1) and placebo IV (Day 3)

Drug: granisetron

Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3

Other Names:

Granisetron Transdermal System

Sancuso® patch

Kytril®

Granisetron Injection

IV Placebo (0.9% saline)

Placebo patches

Avelox® Oral

Active Comparator: Treatment D: Oral Moxifloxacin 400 mg

Treatment D: placebo patch (Day 1) and oral moxifloxacin (Day 3).

Drug: granisetron

Treatment A: Sancuso® patch (3.1mg/24 hours) on Day 1 and IV placebo (0.9% saline) on Day 3 Treatment B: Granisetron IV 10 mcg/kg over 30 seconds on Day 1 and placebo patch on Day 3 Treatment C: Placebo patch on Day 1 and IV placebo on Day 3 Treatment D: 400 mg oral moxifloxacin on Day 1 and placebo patch on Day 3

Relationship of plasma concentration of granisetron versus QTcF, both graphical and mixed effects analyses of plasma concentration of granisetron versus QTcF will be performed [ Time Frame: 0 to 120 hours post-dose ]

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Ages Eligible for Study:

18 Years to 50 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Criteria

Inclusion Criteria:

Healthy male or female subjects

Aged between 18 and 50 years, inclusive, at screening

BMI between 18.0 and 32.0 kg/m², inclusive

Exclusion Criteria:

History of drug abuse

Known hypersensitivity to granisetron, moxifloxacin, or related compounds, such as ciprofloxacin and levofloxacin

Abnormal Screening ECG indicating a second- or third degree AV block, or one or more of the following: QRS >120 milliseconds (ms); QTcF > 430 (males) or 450 (females) ms; PR interval >240 ms; any rhythm, other than sinus rhythm, interpreted to be clinically significant by the Investigator

Known history of long-QT syndrome, angina, myocardial ischemia or infarction, congestive heart failure, myocarditis, chest pain or dyspnea on exertion

Electrolyte disturbances (such as uncorrected hypokalemia/hyperkalemia, hypomagnesemia, hypocalcemia, or hypophosphatemia), idiopathic cardiomyopathy, unexplained syncope, hypertrophic cardiomyopathy, or sudden unexplained death at a young age (< 40 years) in a first-degree relative.

Has used any medications or consumed any foods contraindicated in the protocol.